Retinal edema is a commonly encountered and potentially sight-threatening complication of vascular retinopathies in man. Ophthalmoscopic and fluorescenin angiographic observations in patients provide useful information, but little is known concerning permeability mechanisms of the development, resolution and especially non-resolution of retinal edema. We propose to identify mechanisms of acute and chronic retinal edema in older normotensive and spontaneously hypertensive rats with laser-induced branch retinal vein occlusion (BRVO) and sodium iodate-induced retinal pigment epithelial (RPE) damage. In man, BRVO is the 2nd most frequently encountered vascular retinopathy, it occurs most commonly in hypertensive patients, and chronic (cystoid) retinal edema has frequent association with histologic abnormalities of the RPE. Our animal model is designed to work within the human clinical circumstances. Vitreous fluorophotometry and computer-assisted quantitative fluorescence microscopy will identify the developing. resolving or non-resolving phases of the retinal edema. Selected combinations of fluorescent labeled proteins and non-proteins (e.g. FITC-dextrans, Evans-blue serum albumin complex, FITC-IgG) can be analysed in the same tissue sample regarding the composition and constituent concentrations of the edema fluid. These data, by identifying the various edematous phases, will provide a basis for ultrastructural analysis of associated permeability mechanisms. Electron dense tracers of selected sizes will allow correlation of ultrastructural permeability data to the fluorophotometric data and assess the role of vesicular transport and/or opened endothelial/RPE cell junctions as mechanisms. Morphometry will provide in depth analysis of vesicular transport, endothelial/RPE cell volume and surface area, Muller cell volume and extracellular space alterations. Our studies will continue developing an understanding of abnormal permeability mechanisms in acute and chronic edema. Understanding those morphologic aspects of retinal edema will provide a basis for investigating transport mechanisms with biochemical and physiologic techniques, and for developing models for effectively studying retinal and macular edema in non-human primates. Finally, these studies will provide a basis for assessing the efficacy of therapeutic modalities to alleviate or prevent retinal edema.